Gamma-hydroxybutyric acid binding sites in rat and human brain synaptosomal membranes

The binding of gamma-hydroxy[2,3-3H]butyric acid (GHB) was characterized in rat and human brain synaptosomal membranes. Binding was shown to be saturable, pH dependent, and linear with protein concentration. There was a distinct regional distribution of binding sites in both rat and human brain, with the hippocampus being the richest and the cerebellum the poorest, in density of [3H]GHB binding sites. Competition and saturation experiments revealed two different population of binding sites, a high-affinity site with a KD1 of 580 nM and a B max1 of 1.8 pmoles/mg protein and a low-affinity site with a KD2 of 2.3 microM and a B max2 of 11.3 pmoles/mg protein. [3H]GHB binding was not inhibited by gamma-aminobutyric acid (GABA), GABA receptor agonists, opiate antagonists or anticonvulsant drugs. These data suggest that GHB may play a role as a neurotransmitter or neuromodulator in brain independent of GABA.